Validation studies of new Positron Emission Tomography (PET) methodologies have been initiated in two areas: (1) 68Ga-EDTA as a tracer to determine regional brain plasma volume (Vp), capillary permeability or transfer constants (K) and estimates of the extracellular space (ECS); (2) 18F-Acetylcyclofoxy, and analogue of the narcotic anatagonist naltrexone, as a potential ligand with high affinity to opiate receptors in vivo. 1. 68Ga-EDTA. Concurrent studies using 68G-EDTA(PET) and 14C-A1B or 14C-EDTA (quantitative autoradiography) were performed in dogs with brain tumors. The time-activity PET data was fitted to a compartment model to yield values of Vp, K and ECS and compared to the estimate of K and EDTA tissue activity obtained autoradiographically in the same animal. On the basis of these studies an IND has been filed with the FDA and a protocol involving the study of patients with glioblastoma has been initiated. 2. 18F-Acetylcyclofoxy. Time-activity studies (PET) have been performed in baboons and localization was clearly demonstrated in "opiate-rich" areas of the brain (e.g., basal ganglia and thalamus). Displacement of the ligand from these areas using the opiate antagonist, naloxone, was very rapid and suggests specific ligand-opiate receptor interaction. A kinetic model and analysis of the data is being developed.